Table 5.

Most Frequently Reported Adverse Events That Occurred during the Study Period.^*

Event	European Union Trial		U.S. Trial
	Afamelanotide (N = 38)	Placebo (N = 36)	Afamelanotide (N = 48)	Placebo (N = 45)
Total no. of events	189	166	272	216
Ear and labyrinth disorder: ear pain — no. (%)	1 (3)	2 (6)	2 (4)	0
Gastrointestinal disorder — no. (%)
Abdominal discomfort	0	1 (3)	1 (2)	2 (4)
Abdominal pain	4 (11)	1 (3)	1 (2)	3 (7)
Upper abdominal pain	1 (3)	1 (3)	1 (2)	3 (7)
Diarrhea	3 (8)	4 (11)	2 (4)	3 (7)
Dyspepsia	0	1 (3)	3 (6)	3 (7)
Nausea	7 (18)	6 (17)	9 (19)	8 (18)
Toothache	0	0	3 (6)	3 (7)
Vomiting	1 (3)	2 (6)	1 (2)	0
General disorder and administration-site condition — no. (%)
Fatigue	1 (3)	2 (6)	3 (6)	0
Implant-site discoloration	4 (11)	0	9 (19)	0
Pain	0	0	4 (8)	4 (9)
Infection and infestation — no. (%)
Viral gastroenteritis	1 (3)	2 (6)	0	3 (7)
Influenza	6 (16)	3 (8)	2 (4)	7 (16)
Nasopharyngitis	8 (21)	8 (22)	6 (12)	10 (22)
Sinusitis	0	2 (6)	3 (6)	3 (7)
Upper respiratory tract infection	3 (8)	1 (3)	1 (2)	0
Abnormal laboratory result — no. (%)
Blood in urine	2 (5)	2 (6)	0	0
Increase in γ-glutamyltransferase level	0	3 (8)	0	0
Musculoskeletal and connective-tissue disorder — no. (%)
Arthralgia	0	2 (6)	5 (10)	2 (4)
Back pain	2 (5)	4 (11)	6 (12)	6 (13)
Musculoskeletal pain	0	1 (3)	3 (6)	1 (2)
Myalgia	1 (3)	2 (6)	3 (6)	1 (2)
Pain in extremity	1 (3)	2 (6)	2 (4)	2 (4)
Nervous system disorder — no. (%)
Dizziness	0	0	1 (2)	2 (4)
Headache	13 (34)	14 (39)	19 (40)	13 (29)
Migraine	1 (3)	3 (8)	3 (6)	3 (7)
Sinus headache	0	0	1 (2)	2 (4)
Respiratory, thoracic, and mediastinal disorder — no. (%)
Cough	5 (13)	2 (6)	1 (2)	1 (2)
Oropharyngeal pain	6 (16)	2 (6)	2 (4)	2 (4)
Skin and subcutaneous tissue disorder — no. (%)
Eczema	2 (5)	1 (3)	0	1 (2)
Melanocytic nevus	0	0	2 (4)	1 (2)
Pigmentation disorder	3 (8)	0	1 (2)	0
Pruritus	2 (5)	1 (3)	2 (4)	2 (4)

^*Events listed were reported by three or more patients in either of the studies.